Werk Tobias, Ludwig Imke S, Mahler Hanns-Christian, Luemkemann Joerg, Huwyler Joerg, Hafner Mathias
Pharmaceutical Technology, University of Basel, Basel, Switzerland;
Pharmaceutical Development & Supplies, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
PDA J Pharm Sci Technol. 2016;70(6):508-522. doi: 10.5731/pdajpst.2016.006387.
Reconstitution time of dried products is influenced by various factors including formulation, process, and reconstitution method itself. This manuscript describes factors affecting reconstitution in a dual chamber syringe using highly concentrated human monoclonal antibody and bovine serum albumin model formulations. Freezing and drying conditions had only minor impact on the reconstitution time, whereas the primary container and thus the geometry of the lyophilization cake played a major role. Prewarmed diluent and agitation decreased reconstitution time. For effective agitation, short displacements and high agitation frequencies were found to be desirable conditions to minimize reconstitution time for a given lyophilization cake while foam formation was minimized. The article also provides general strategies (e.g., reduction of lyophilized cake density, use of an optimized fill finish process, and suitable method parameters) to reduce reconstitution time, especially for drug product presented in a dual chamber syringe configuration.
Dried drug products need to be reconstituted to a liquid form before being applied parenteral. Reconstitution time is an important attribute and needs to be as fast as possible in order to serve patients' compliance. Reconstitution time is influenced by various factors including formulation, process, and the reconstitution method itself. The article provides general strategies (e.g., reduction of dried drug product cake density, use of an optimized fill finish process, and suitable method parameters) to reduce reconstitution time, especially for drug product presented in a dual chamber syringe. Fast reconstitution of lyophilisates in dual chamber syringe can be achieved by a combination of optimized manufacturing procedures and clear instructions for the end-user (e.g., roll syringe between palms to warm and agitate it to accelerate reconstitution).
干燥产品的复溶时间受多种因素影响，包括制剂、工艺和复溶方法本身。本手稿描述了使用高浓度人单克隆抗体和牛血清白蛋白模型制剂的双腔注射器中影响复溶的因素。冷冻和干燥条件对复溶时间的影响较小，而主要容器以及冻干饼的几何形状起主要作用。预热稀释剂和搅拌可缩短复溶时间。对于有效的搅拌，短位移和高搅拌频率是在给定冻干饼的情况下使复溶时间最短同时使泡沫形成最小化的理想条件。本文还提供了一般策略（例如，降低冻干饼密度、采用优化的灌装完成工艺和合适的方法参数）来缩短复溶时间，特别是对于双腔注射器配置的药品。
干燥的药品在肠胃外给药前需要复溶成液体形式。复溶时间是一个重要属性，为了符合患者的依从性，需要尽可能快。复溶时间受多种因素影响，包括制剂、工艺和复溶方法本身。本文提供了一般策略（例如，降低干燥药品饼的密度、采用优化的灌装完成工艺和合适的方法参数）来缩短复溶时间，特别是对于双腔注射器配置的药品。通过优化的制造程序和为最终用户提供清晰的说明（例如，在手掌间滚动注射器以加热和搅拌以加速复溶），可以实现双腔注射器中冻干物的快速复溶。
